To investigate the effects of mycophenolate mofetil (MMF) on the process of renal interstitial fibrosis, unilateral ureteral obstruction (UUO) model was established in rats. Twenty Sprague-Dawley rats underwent UUO and received vehicle (n = 10) or MMF (20 mg.kg-1.d-1, by daily gastric gavage, n = 10) during a period of 5 days following surgery, and the additional 10 rats were served as sham-operated group. The rats were killed 5 days after surgery. Immunohistochemistry was performed on renal tissue for proliferating cell nuclear antigen (PCNA), alpha-smooth muscle actin (alpha-SMA) and type I and III collagen (col I, col III). Histological studies were also done by MASSON staining. Five days after surgery, proliferating cells in tubules, interstitium as well as interstitial myofibroblast (MyoF) infiltration and interstitial col I, col III deposition were all significantly reduced by MMF treatment. MMF also alleviated the histological changes of UUO rats. These results suggested that the reduction of interstitial MyoF infiltration may be an important event by which MMF prevents renal injury caused by UUO and MMF could be used to limit the progression of renal fibrosis.
Fibrosis ; Kidney/*pathology ; Kidney Diseases/etiology ; Kidney Diseases/pathology ; Kidney Diseases/*prevention & control ; Mycophenolic Acid/*analogs & derivatives ; Mycophenolic Acid/*pharmacology ; Random Allocation ; Rats, Sprague-Dawley ; Ureteral Obstruction/*complications

Child, Preschool ; Female ; Humans ; Infant ; Male ; Mycophenolic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Nephrotic Syndrome ; drug therapy ; Treatment Outcome

AIMTo investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients.

METHODSThirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software.

RESULTSThe plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients.

CONCLUSIONIn view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.

Adult ; Aged ; Area Under Curve ; Female ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Liver Transplantation ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; pharmacokinetics

OBJECTIVETo analyze the clinical features of mid- and long-term acute cardiac allograft rejection to improve the long-term clinical outcomes of the patients.

METHODSFourteen recipients (11 males and 3 females) underwent orthotopic heart transplantation with standard immunosuppressive therapy protocols (3 cases) or induction therapy protocols (11 cases). Cyclosporine, azathioprine or mycophenolate mofetil, and prednisolone were applied as the maintenance immunosuppressive regimen. Acute graft rejection episodes occurred within 3 to 6 months in 1 case, within 6 months to 1 year in 3 cases, within 1 to 2 years in 3 cases, within 2 to 5 years in 6 cases, and above 5 years in 1 case.

RESULTSNo significant difference was found in the incidence of late heart rejection between the patients receiving the two immunosuppressive therapy protocols. Immunosuppressants were withdrawn or spared in 8 recipients due to different causes. Nine recipients with steroid-sensitive acute cardiac allograft rejection were treated with steroid-pulse therapy, while the other 5 were treated with a short course of polyclonal antithymocyte antibodies because of steroid-resistant acute rejection; in 11 cases, azathioprine was converted to mycophenolate mofetil. Four of the 5 late deaths occurred in the recipients with steroid-resistant rejection. The surviving recipients had a good quality of life, and no recurrent episodes of rejection or infection were observed in the follow-up period.

CONCLUSIONSLate acute cardiac allograft rejection is associated mainly with patient compliance but not with early immunosuppressive therapy protocols. The episodes are rather severe and should be timely treated with steroid pulses or polyclonal antithymocyte antibodies.

Adolescent ; Adult ; Cyclosporine ; Female ; Graft Rejection ; etiology ; prevention & control ; Heart Transplantation ; adverse effects ; Humans ; Immunosuppression ; methods ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; Young Adult

To investigate the effects of mycophenolate mofetil (MMF) on the process of renal interstitial fibrosis, unilateral ureteral obstruction (UUO) model was established in rats. Twenty Sprague-Dawley rats underwent UUO and received vehicle (n = 10) or MMF (20 mg.kg-1.d-1, by daily gastric gavage, n = 10) during a period of 5 days following surgery, and the additional 10 rats were served as sham-operated group. The rats were killed 5 days after surgery. Immunohistochemistry was performed on renal tissue for proliferating cell nuclear antigen (PCNA), alpha-smooth muscle actin (alpha-SMA) and type I and III collagen (col I, col III). Histological studies were also done by MASSON staining. Five days after surgery, proliferating cells in tubules, interstitium as well as interstitial myofibroblast (MyoF) infiltration and interstitial col I, col III deposition were all significantly reduced by MMF treatment. MMF also alleviated the histological changes of UUO rats. These results suggested that the reduction of interstitial MyoF infiltration may be an important event by which MMF prevents renal injury caused by UUO and MMF could be used to limit the progression of renal fibrosis.
Animals ; Female ; Fibrosis ; Kidney ; pathology ; Kidney Diseases ; etiology ; pathology ; prevention & control ; Mycophenolic Acid ; analogs & derivatives ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications

Adolescent ; Adult ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Severity of Illness Index ; Treatment Outcome

BACKGROUNDMycophenolic acid (MPA) as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation. This study aimed to investigate the pharmacokinetic (PK) characteristics of enteric-coated mycophenolate sodium (EC-MPS) and area under the curve (AUC) from 0 to 12 hours with limited sampling strategies (LSSs) in Chinese renal transplant recipients.

METHODSThis study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS, cyclosporine, and corticosteroids. MPA concentrations were measured by enzyme multiplied immunoassay technique (EMIT). Whole 12-hour PK profiles were obtained on Day 4 after operation. LSSs with jackknife technique, multiple stepwise regression analysis, and Bland-Altman analysis were developed to estimate MPA AUC.

RESULTSThe mean maximum plasma concentration, the mean time for it to reach peak (T(max)), and the mean MPA AUC were (11.38 ± 2.49) mg/L, (4.85 ± 3.32) hours, and (63.19 ± 13.54) mg×h×L(-1), respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding T(max) was significantly longer than that of the other six patients. No patient exhibited a second peak caused by enterohepatic recirculation. The best models were as follows: 27.46 + 0.94C(3) + 3.24C(8) + 2.81C(10) (r(2) = 0.972), which was used to predict AUC of fast metabolizer with a mean prediction error (MPE) of -0.21% and a mean absolute prediction error (MAE) of 2.59%; 36.65 + 3.08C(8) + 5.30C(10) - 4.04C(12) (r(2) = 0.992), which was used to predict AUC of slow metabolizer with a MPE of 0.58% and a MAE of 1.95%.

CONCLUSIONSThe PKs of EC-MPS had a high variability among Chinese renal transplant recipients. The preliminary PK data indicated the existence of slow and fast metabolizer. These findings may be associated with the enterohepatic recirculation.

Adrenal Cortex Hormones ; therapeutic use ; Adult ; Aged ; Cyclosporine ; therapeutic use ; Female ; Humans ; Kidney Transplantation ; methods ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Young Adult

This study was purposed to evaluate the curative efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) after failure of the first allo-HSCT in aplastic anemia patients, the cause of implant failure after allo-HSCT and clinical data of 10 severe aplastic anemia (SAA) patients in the second allo-HSCT were retrospectively analyszed. The second HSCT conditioning programs include: cyclophosphamide (CTX) + fludarabine (FLU)+ anti-thymocyte globulin (ATG) combination chemotherapy for 3 cases; CTX + FLU + white busulfan (Bu) + ATG combination chemotherapy for 7 cases. The prevention regimen of graft-versus-host disease (GVHD) include cyclosporine (CsA), mycophenolate mofetil (MMF) and methotrexate (MTX). The median count of mononuclear cell infusion was 12.17 (5.99-18.12)×10(8)/kg. The CD34(+) cell count was 5.2 (3.8-10.9)×10(6)/kg. The results showed that 10 evaluable patients achieved hematopoietic reconstitution with absolute neutrophil >0.5×10(9)/L, platelets >20×10(9)/L at 15d (8-21d) and 17d (11-27d) after transplantation. The grade I aGVHD occurred in 2 case, grade II in 1 case, chronic GVHD in 3 cases. Transplant-related deaths occurred in 4 cases. The disease-free survival rate, transplant-related mortality, GVHD after transplantation were 60%, 40% and 50% respectively. It is concluded that the second allo-HSCT is an effective therapy for aplastic anemia after allo-HSCT implant failure.
Allografts ; Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Methotrexate ; Mycophenolic Acid ; analogs & derivatives ; Retrospective Studies

Animals ; BCG Vaccine ; Immunosuppressive Agents ; therapeutic use ; Lipopolysaccharides ; Liver Failure ; chemically induced ; prevention & control ; Male ; Mice ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use

BACKGROUNDMycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases. However, whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases, such as endocapillary proliferation, cellular crescents, and/or capillary loops fibrinoid necrosis is still unknown. We, therefore, initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.

METHODSOne hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled. All patients were treated with prednisone; 48 patients received prednisone only (Pred group), 40 received MMF and prednisone (MMF + Pred group), and 31 were treated with CTX and prednisone (CTX + Pred group). The median time of follow-up was 30 months (maximum: 96 months). The primary endpoint was defined as renal survival. The incidence of remission of proteinuria was the secondary endpoint.

RESULTSSerum creatinine in all groups declined significantly at different follow-up times (P = 0.002), and the differences among the three groups were significant (P < 0.001). At 24 months of follow-up, the decline rates were 12.35%, 32.95%, and 24.14% in the Pred, MMF + Pred, and CTX + Pred groups respectively. For urine protein excretion, the decline rates were 49.12% (Pred), 73.67% (MMF + Pred), and 63.53% (CTX + Pred) respectively at 24 months of follow-up. The differences among the three groups were not significant (P = 0.714). Renal survival (the primary endpoint) was significantly different (P = 0.027); however, the sencondary endpoint was similar for all the three groups (P = 0.100).

CONCLUSIONSFor IgA nephropathy patients with endocapillary proliferation, cellular crescents, and/or fibrinoid necrosis of capillary loops, prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX. Combined MMF and prednisone treatment led to a better renal survival compared to that of prednisone with CTX.

Adult ; Female ; Glomerulonephritis, IGA ; drug therapy ; pathology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Retrospective Studies ; Young Adult